Potential therapeutic targets for growth arrest of colorectal cancer cells exposed to PTHrP

Martín, María Julia; Gigola, Graciela; Zwenger, Ariel Osvaldo; Carriquiriborde, Martín; Gentil, Florencia; Gentili, Claudia

doi:10.1016/j.mce.2018.07.005

Cited by 10 publications

(30 citation statements)

References 74 publications

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“…We evaluated if the response of HMEC-1 cells observed previously by us is the same or is different when these cells were exposed to TCMs which were pre-incubated for h at °C with the anti-VEGF antibody or with an appropriate isotype-matched control rabbit IgG. As shown in Figures 6A, B In previous studies, we obtained evidence that the hormone increases the proliferation, migration, survival and chemoresistance via MAPKs and PI3K/AKT signaling pathways in the colon cancer Caco-2 cells and HCT116 cells (Lezcano et al, 2013;Martín et al, 2014;Calvo et al, 2014;Calvo et al, 2017;Martín et al, 2018). ERK1/2 and AKT are central proteins in many cellular pathways leading to angiogenesis (Xu et al, 2015;Dong et al, 2017).…”

Section: Pthrp Promotes Tumor Angiogenesis Mainly Through Vegfsupporting

confidence: 61%

“…CRC is one of the main causes of death for cancer in the world (Siegelet al, 2017). chemoresistance and has a protective effect in conditions of apoptosis by the regulation of these signaling pathways (Lezcano et al, 2013;Martín et al, 2014;Calvo et al, 2014;Calvo et al, 2017;Martín et al, 2018). We think that other…”

Section: Discussionmentioning

confidence: 97%

“…Several of the signaling pathways that may participate in the regulation of proangiogenic factors (Xu et al, 2015;Hammoud et al, 2016;Dong et al, 2017) are modulated by PTHrP in cells derived from CRC (Lezcano et al, 2013;Martín et al, 2014;Calvo et al, 2014;Calvo et al, 2017;Martín et al, 2018). Figure 1A).…”

Section: Pthrp Increases Vegf Expression and The Number Of Structuresmentioning

confidence: 99%

“…Recently, we found that PTHrP induces chemoresistance in Caco-2 and HCT116 cells through mitogenic signaling pathways such ERK and Akt (Martin et al, 2018). Also, the administration of PTHrP in HCT xenografts of nude mice, increased the expression of RSK and others markers related to tumorigenic events (Calvo et al, 2017;Martín et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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PTHrP treatment of colon cancer cells promotes tumor associated-angiogenesis by the effect of VEGF

Calvo

Carriere

Martín

et al. 2019

Molecular and Cellular Endocrinology

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We showed that Parathyroid Hormone-related Peptide (PTHrP) induces proliferation, migration, survival and chemoresistance via MAPKs and PI3K/AKT pathways in colorectal cancer (CRC) cells. The objective of this study was to investigate if PTHrP is also involved in tumor angiogenesis. PTHrP increased VEGF expression and the number of structures with characteristics of neoformed vessels in xenografts tumor. Also, PTHrP increased mRNA levels of VEGF, HIF-1α and MMP-9 via ERK1/2 and PI3K/Akt pathways in Caco-2 and HCT116 cells. Tumor conditioned media (TCMs) from both cell lines treated with PTHrP increases the number of cells, the migration and the tube formation in the endothelial HMEC-1 cells, whereas the neutralizing antibody against VEGF diminished this response. In contrast, PTHrP by direct treatment only increased ERK1/2 phosphorylation and the HMEC-1 cells number. These results provide the first evidence related to the mode of action of PTHrP that leads to its proangiogenic effects in the CRC. Highlights: PTHrP has indirect proangiogenic effects in the CRC via VEGF. PTHrP mediates the interaction of colon tumor cells with the endothelial cells. PTHrP does not stimulate directly migration neither tube formation of endothelial cells.

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Section: Pthrp Promotes Tumor Angiogenesis Mainly Through Vegfsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 97%

Section: Pthrp Increases Vegf Expression and The Number Of Structuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PTHrP treatment of colon cancer cells promotes tumor associated-angiogenesis by the effect of VEGF

Calvo

Carriere

Martín

et al. 2019

Molecular and Cellular Endocrinology

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“…By the implementation of multiple assays, we found that PTHrP (1-34) stimulates the cell cycle progression and proliferation of Caco-2 cells[ 37 , 38 ]. In line with these results, we reported similar effects induced by the cytokine in HCT116 cells, a CRC-derived cell line more undifferentiated and aggressive concerning Caco-2 cells, which also expresses PTHR1[ 39 ]. Despite the notable differences between Caco-2 cell and HCT116 cell phenotypes, the molecular mechanisms leading to these responses to the peptide in both CRC cells were similar and implied the activation of well-known deregulated pathways in CRC.…”

Section: Pthrp Promotes Cell Cycle Progression Proliferation and Migration Of Crc Cellssupporting

confidence: 62%

Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells

Díaz¹,

Carriere²,

Martín³

et al. 2021

WJG

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Colorectal cancer (CRC) remains one of the leading causes of mortality from malignant diseases worldwide. In general terms, CRC presents high heterogeneity due to the influence of different genetic and environmental factors; also, the neoplastic cells are strongly influenced by the extracellular matrix and several surrounding cells, known together as the tumor microenvironment (TME). Bidirectional communication takes place between the tumor and the TME through the release of autocrine and paracrine factors. Parathyroid hormone-related peptide (PTHrP) is a cytokine secreted by a wide variety of tissues and is able to regulate several cellular functions both in physiological as well as in pathological processes. It exerts its effects as a paracrine/autocrine factor, although its mode of action is mainly paracrine. It has been shown that this peptide is expressed by several tumors and that the tumor secretion of PTHrP is responsible for the malignant humoral hypercalcemia. Eight years ago, when our research group started studying PTHrP effects in the experimental models derived from intestinal tumors, the literature available at the time addressing the effects of PTHrP on colorectal tumors was limited, and no articles had been published regarding to the paracrine action of PTHrP in CRC cells. Based on this and on our previous findings regarding the role of PTH in CRC cells, our purpose in recent years has been to explore the role of PTHrP in CRC. We analyzed the behavior of CRC cells treated with exogenous PTHrP, focalizing in the study of the following events: Survival, cell cycle progression and proliferation, migration, chemoresistance, tumor-associated angiogenesis, epithelial to mesenchymal transition program and other events also associated with invasion, such us the induction of cancer stem cells features. This work summarizes the major findings obtained by our investigation group using in vitro and in vivo CRC models that evidence the participation of PTHrP in the acquisition of an aggressive phenotype of CRC cells and the molecular mechanisms involved in these processes. Recently, we found that this cytokine induces this malignant behavior not only by its direct action on these intestinal cells but also through its influence on cells derived from TME, promoting a communication between CRC cells and surrounding cells that contributes to the molecular and morphological changes observed in CRC cells. These investigations establish the basis for our next studies in order to address the clinical applicability of our findings. Recognizing the factors and mechanisms that promote invasion in CRC cells, evasion to the cytotoxic effects of current CRC therapies and thus metastasis is decisive for the identification of new markers with the potential to improve early diagnosis and/or to predict prognosis, to predetermine drug resistance and to provide treatment guidelines that include targeted therapies for this disease.

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Doxorubicin delivery by magnetic nanotheranostics enhances the cell death in chemoresistant colorectal cancer-derived cells

Martín

Azcona

Lassalle

et al. 2021

European Journal of Pharmaceutical Sciences

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Potential therapeutic targets for growth arrest of colorectal cancer cells exposed to PTHrP

Cited by 10 publications

References 74 publications

PTHrP treatment of colon cancer cells promotes tumor associated-angiogenesis by the effect of VEGF

PTHrP treatment of colon cancer cells promotes tumor associated-angiogenesis by the effect of VEGF

Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells

Doxorubicin delivery by magnetic nanotheranostics enhances the cell death in chemoresistant colorectal cancer-derived cells

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